Hydroxypropyl Methylcellulose K4M Research Articles

ESTIMATION OF BACOSIDE-A IN BACOPA MONNIERI AERIAL PARTS USING TLC DENSITOMETRY

Objective: The objective of the present work was to formulate and evaluate a stable, odour free garlic powder loaded floating matrix tablet for the treatment of peptic ulcers.
 Methods: A gastro-retentive floating matrix tablet (FMT) formulation of garlic powder (GP) was prepared using various concentrations of hydroxypropyl methylcellulose K4M (HPMC K4 M) and effervescent system (sodium bicarbonate and citric acid in 1:1 % w/w) to achieve desirable floating time (FT), floating lag time (FLT) and drug release. Wet granulation method was selected using ethanol as a binder for preparation of tablet. 32 full factorial designs were used for selection of suitable polymer concentration and effervescent system. Nonenteric film coating was applied to mask GP odour.
 Results: It was observed that FMT with optimum quantities of HPMC K4M and the effervescent system showed 97 % of drug release in 12 h with FT up to 10 h and minimum FLT of 3 min. There was no significant change in FLT, FT and drug content during the stability study of FMT.
 Conclusion: A stable, sustained release FMT of GP tablets using HPMC K4M and an effervescent system was successfully prepared. This formulation can overcome problems of taste and odour masking, gastric irritation, and loss of active constituents present in garlic.

FORMULATION AND EVALUATION OF GARLIC POWDER LOADED FLOATING MATRIX TABLET

Objective: The objective of the present work was to formulate and evaluate a stable, odour free garlic powder loaded floating matrix tablet for the treatment of peptic ulcers.
 Methods: A gastro-retentive floating matrix tablet (FMT) formulation of garlic powder (GP) was prepared using various concentrations of hydroxypropyl methylcellulose K4M (HPMC K4 M) and effervescent system (sodium bicarbonate and citric acid in 1:1 % w/w) to achieve desirable floating time (FT), floating lag time (FLT) and drug release. Wet granulation method was selected using ethanol as a binder for preparation of tablet. 32 full factorial designs were used for selection of suitable polymer concentration and effervescent system. Nonenteric film coating was applied to mask GP odour.
 Results: It was observed that FMT with optimum quantities of HPMC K4M and the effervescent system showed 97 % of drug release in 12 h with FT up to 10 h and minimum FLT of 3 min. There was no significant change in FLT, FT and drug content during the stability study of FMT.
 Conclusion: A stable, sustained release FMT of GP tablets using HPMC K4M and an effervescent system was successfully prepared. This formulation can overcome problems of taste and odour masking, gastric irritation, and loss of active constituents present in garlic.

3D Printing and Characterization of Hydroxypropyl Methylcellulose and Methylcellulose for Biodegradable Support Structures

Abstract Additive manufacturing process based on fused deposition modeling (FDM) and material extrusion (ME) typically use thermoplastic materials like ABS, PLA, or nylon to fabricate parts layer-by-layer. In order to build a part successfully with complex features such as pores or holes or irregular shapes, the build part requires support structures to hold the deposited material and to prevent collapse of the finished parts before solidification. The support material acts as a sacrificial layer that should be easily removed later on by chemicals/enzymes, or broken by mechanical force. The present support materials used with FDM technology have challenges of poor dissolvability in chemical solution and difficulty to be removed from the finished part. In addition, these support materials are usually petroleum based which has a negative impact on the environment. The goal of the project is to identify a suitable biomaterial for support structures that will eliminate the challenges of poor dissolvability and toxic waste generated by the current material. This paper is focused on extrusion-based 3D printing process of thermoset biopolymers to fabricate support structures. In this study, three biodegradable cellulose derivatives, i.e. methylcellulose (MC) A4M, HPMC K4M, and hydroxypropyl methylcellulose (HPMC) E4M, with different degree of substitution of hydroxyl group were used. We investigated the effect of concentrations (8, 10, and 12% w/v) of all three cellulose derivatives on the rheological properties for understanding their printability. The rheological analysis revealed that all hydrogels exhibit shear-thinning properties with relatively low yield stress. At the same concentration, the apparent viscosity of HPMC K4M tended to be higher than HPMC E4M, followed by MC A4M. Effects of printing parameters (extrusion rate, nozzle diameter, and printing speed) were optimized to obtain the desired three-dimensional structures. The sample of 12% MC A4M and 12% w/v HPMC K4M showed higher complex shear modulus than other materials, which indicated higher rigidity and shape retention capacity of the printed parts. The ideal material for extrusion during printing and least deformation after printing was also observed for 12% MC A4M, which indicated a relationship between rheological properties and printability. The water dissolution of the MC and HPMC hydrogels allowed easy removal of the support structures from the build material. Biopolymers like MC and HPMC, when 3D printed as a support material via ME processes, help in moving closer towards sustainable manufacturing.

Solid Sirolimus Self-microemulsifying Drug Delivery System: Development and Evaluation of Tablets with Sustained Release Property.

The clinical application of sirolimus (SRL) as an immunosuppressive agent is largely hampered by its narrow therapeutic range. This study focused on developing SRL tablets with a sustained release profile for better safety. SRL was highly water insoluble and its solubility has been efficiently enhanced by preparing self-microemulsifying drug delivery system (SMEDDS). The SRL-SMEDDS was physically adsorbed by microcrystalline cellulose (MCC). The sustained release of SRL was achieved by addition of hydroxypropyl methylcellulose (HPMC) to prepare tablets. The formulation of the tablets was optimized by single factor test and orthogonal design. The optimal formulation was composed of 10% of HPMC 100lv and 5% of HPMC K4M. The in-vitro release profiles of the optimal tablets were further investigated for the influence of hardness, shape, preparing method, release method, stirring speed, and medium. The release kinetic of SRL from the tablets was demonstrated to be erosion of HPMC. Pharmacokinetic study on beagle dogs showed that the SRL-SMEDDS tablets were bio-equivalent to the commercial tablets but lower Cmax and larger Tmax were achieved. In conclusion, the SMEDDS tablets were presented as promising delivery system for sustained release of SRL.

DESIGN AND DEVELOPMENT OF GASTRORETENTIVE DRUG DELIVERY SYSTEM OF CIPROFLOXACIN HYDROCHLORIDE

Objective: The aim is to prepare the floating tablet of ciprofloxacin and to improve their bioavailability in the treatment against the Gram-positive and Gram-negative microorganisms. Ciprofloxacin HCL is an acidic drug used for respiratory tract infection, diarrhea, skin infection, thyroid fever, and urinary tract infection. The ciprofloxacin HCL is primarily absorbed in the stomach and it has low bioavailability. Due to its low availability, it was chosen as an appropriate drug for the scheme of the gastroretentive floating drug delivery system. Method: Ciprofloxacin HCl is an acidic drug which was made by wet granulation process using various polymers, which include hydroxypropyl methylcellulose K4M, Eudragit, and Guar gum with a different composition. The gas generating agents such as saleratus and citric acid were used for the preparation. The prepared granules were subjected to pre-compression parameters technique and the formulated tablets were subjected to post-compression parameters, respectively. Result: The Fourier-transform infrared analysis reveal that the drug and excipients used for the formulations were compatible with each other. All formulated granules having good flow properties and all the post-compression parameter are within the limit in which the F4 formulation shows optimum drug release of about 98.7% at 12 h and which has the buoyancy lag time of about 134 s and floating time about 12.5 h. Kinetic treatment revealed of the optimized preparation is based on Korsmeyer–Peppas model. The value n=0.861 states the process of non-Fickian diffusion. Conclusion: Based on above observation found in the work, it was concluded that ciprofloxacin HCl can formulate as a floating drug delivery system which helps in increasing the gastric residence time, as a result, it increases the bioavailability and half-life of ciprofloxacin HCl.

DESIGN AND IN VITRO/IN VIVO EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF NATEGLINIDE

Aim: Nateglinide is a quick acting anti-diabetic medication whose potent activity lasts for a short duration. One of the dangerous side effects of nateglinide administration is rapid hypoglycemia, a condition that needs to be monitored carefully to prevent unnecessary fatalities. The aim of the study was to develop a longer lasting and slower releasing formulation of nateglinide that could be administered just once daily.
 Methods: Matrix tablets of nateglinide were prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC), eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release patterns were evaluated using in vitro and in vivo studies.
 Conclusion: Of the seventeen formulated matrix tablets tested, only one formulation labelled HA-2 that contained 15% HPMC K4M demonstrated release profile we had aimed for. Further, swelling studies and scanning electron microscopic analysis confirmed the drug release mechanism of HA-2. The optimized formulation HA-2 was found to be stable at accelerated storage conditions for 3 months with respect to drug content and physical appearance. Mathematical analysis of the release kinetics of HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the sustained drug release profile we had aimed for.
 Keywords: Hydroxypropylmethylcellulose, Matrix tablets, Nateglinide, Sustained release

Formulation and evaluation sustained release mucoadhesive gastroretentive pantoprazole sodium sesquihydrate tablets for anti–ulcer

Objective: The objective of this research work is to develop and evaluate the mucoadhesive gastroretentive tablets of an anti – ulcer drug for sustain release. Materials and Methods: Mucoadhesive tablets were prepared by direct compression method using Hydroxy propyl methyl cellulose K4M, Carbopol 940 NF and Guar gum in the various drug – polymer ratios. The prepared tablets were evaluated for their pre and post compression parameters. In this study the optimized formulation was obtained within the specified limits. Results: The final optimized formulation was showed mucoadhesion time 12 h, mucoadhesive strength of tablets were ready with HPMC K4M, Carbopol 940 NF and gum were found to be 45 g and the extreme proportion of drug release was obtained 97.11% at the completion of 12 h. The drug release mechanism for optimized formulations of pantoprazole mucoadhesive sustain release tablets was observed to be zero order kinetic model. Conclusion: The formulation of hydroxy propyl methyl cellulose showed excellent mucoadhesive ability and a suitable drug release pattern.
 Keywords: Pantoprazole sodium sesquihydrate, Gastroretentive, mucoadhesive polymers

Preparation and in vitro & in vivo evaluation of cephalexin matrix tablets

The purpose of the study is to develop cephalexin controlled-release matrix tablets by using lower proportions of release retardant polymer and to establish their in vitro & in vivo correlation. Tablets were compressed by incorporating polymers in a matrix form along with drug which prolong the drug release. Twelve formulations were prepared by mixing ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) (three different viscosity grades) in various proportions. F-1 to F-4 formulations were prepared by incorporating drug, HPMC K4M and ethyl cellulose in 100 : 5 : 5, 100 : 10 : 5, 100 : 15 : 5 and 100 : 20 : 5; similarly, F-5 to F-8 were prepared with HPMC K15M; and F-9 to F-12 were prepared with HPMC K100M using a wet granulation process maintained same proportions, along with drug and EC. Tablets were evaluated for their pre-compression and post-compression characteristics and they were found to be in limits. From the dissolution testing, F-4 showed 100.34% medicament release in 12 h. In vivo studies were conducted on rabbit and pharmacokinetic parameters of the optimized formulation were evaluated using HPLC method. It was found that matrix tablets showed increased t1/2 and decreased Kel. The design signified that the drug release rate from tablets was influenced by the small proportion (around 7% of a tablet weight) of polymer mixture and it controlled 100% medicament release upto 12 h effectively with the low grade viscosity of HPMC combination, with good in vitro & in vivo correlation.

EFFECTS OF FORMULATION PARAMETERS ON PROPERTIES OF GASTRIC FLOATING TABLETS CONTAINING POORLY SOLUBLE DRUG: DICLOFENAC SODIUM

Objective: The objective of this study was to prepare and investigate the effects of formulation parameters on the properties of gastric floating tablets containing diclofenac sodium (DICL) as a model of poorly soluble acidic drug, sodium bicarbonate (NaHCO3) or calcium carbonate (CaCO3) as gas-forming agent, hydroxypropyl methylcellulose (HPMC) K100M or K15M as swelling polymer and sodium lauryl sulfate (SLS) as wetting agent.Methods: DICL floating tablets were prepared using direct compression method. The compressed tablets were evaluated for tablet properties, swelling index, and in vitro buoyancy. The in vitro release under non-sink condition was determined. Molecular interaction was studied using differential scanning calorimetry and fourier transform infrared spectroscopy.Results: The tablet properties of all DICL floating tablets were within the acceptance criteria. The molecular interaction between DICL and excipients in the formulation was excluded. Depends on the formulation compositions, the swelling index at 3 h (SI) ranged from 44±11 to 1158±33 %, whereas the buoyancy properties namely floating lag time (FLT) and total floating time (TFT) were 0.33±0.03 to 10.04±0.04 min and 10.0±0.0 to>12 h, respectively. NaHCO3 showed higher swelling, buoyancy and release properties compared to those of CaCO3. NaHCO3 at 20% gave sufficient swelling (SI of 1074±16 %), buoyancy (FLT of 0.39±0.03 min, TFT of>12 h) and release properties (cumulative release of 5.83±0.02 %). HPMC K100M showed better swelling property of which its initial swelling rate was 1412±25 %/h compared to HPMC K15M (1042±31 %/h). HPMC K100M at 20% showed better buoyancy and release properties compared to those obtained from HPMC K100M at 30%. The release testing under non-sink conditions was able to distinguish the effect of formulation parameters on the DICL release profiles. Incorporation of SLS at 0.25% could enhance both release rate and cumulative release of DICL from the floating tablets. Nevertheless, it showed the unacceptable adverse effect on swelling and buoyancy properties of DICL floating tablets. The TFT of DICL floating tablets containing 0.25% SLS was only 0.5±0.0 h.Conclusion: DICL floating tablets were successfully prepared. Tablets possessing suitable swelling and buoyancy properties were obtained using NaHCO3 at 20% as a gas-forming agent, with HPMC K100M at 10 and 20% as floating matrix and swelling polymer. Addition of SLS as wetting and solubilizing agent showed the unacceptable adverse effect on the swelling and buoyancy properties of DICL floating tablets. The release under sink conditions and/or in vivo pharmacokinetic studies shall be further performed.

FORMULATION AND IN VITRO EVALUATION OF AMLODIPINE GASTRORETENTIVE FLOATING TABLETS USING A COMBINATION OF HYDROPHILIC AND HYDROPHOBIC POLYMERS

Objective: The aim of this study was to formulate a developed floating tablet of amlodipine using different concentrations and types of hydrophilic and hydrophobic polymers to be conserved in the stomach for modulating solubility and bioavailability, diminishes drug waste and decline side effects.Methods: Through this study, eleven innovative formulations of amlodipine floating tablets were prepared [mixture of amlodipine, sodium bicarbonate (NaHCO3), hydroxypropyl methylcellulose (HPMC) E50, HPMC K100M, ethylcellulose (EC) 5 mp. a. s.] by direct compression method. The pre-compressed mixtures were then evaluated for numerous parameters such as angle of repose, bulk density, tapped density, Carr's compressibility index and Hausner's ratio. After compression, tablets were subjected to several tests like; floating behavior of tablets, tablet thickness, hardness test, friability test, weight variation, in vitro dissolution test. In addition, the optimum formulation was evaluated for Fourier transform-infrared (FT-IR) and differential scanning calorimetry (DSC) tests. Results: From in vitro dissolution tests and kinetic assessments; F8 was selected as an optimum formula, depending on the R2 value of zero order kinetics (0.9915) and (n) value of Korsmeyer-Peppas (0.9635) which indicate purely relaxation zero order kinetic with good delaying in drug release that was reached to 14 h.Conclusion: It can be concluded that the developed formulation of a certain combination of low viscosity grades of HPMC and EC was considered an efficient floating tablet.

Development and pharmacokinetic evaluation of alginate-pectin polymeric rafts forming tablets using box behnken design

Raft is an emerging drug delivery system, which is suitable for controlled release drug delivery and targeting. The present study aimed to evaluate the physico-chemical properties of raft, in vitro release of pantoprazole sodium sesquihydrate and conduct bioavailability studies. Box behnken design was used with three independent and dependent variables. Independent variables were sodium alginate (X1), pectin (X2) and hydroxypropyl methyl cellulose K100M (X3) while dependent variables were percentage drug release at 2 (Y2), 4 (Y4) and 8 h (Y8). The developed rafts were evaluated by their physical and chemical properties. Fourier transform infrared spectroscopy and differential scanning calorimetry were used to study the chemical interaction and thermal behaviour of drug with polymers. Alginate and pectin contents of R9 formulation were 99.28% and 97.29%, respectively, and acid neutralization capacity was 8.0. R9 formulation showed longer duration of neutralization and nature of raft was absorbent. The raft of R9 formulation showed 98.94% release of PSS at 8 h in simulated gastric fluid. Fourier transform infrared spectroscopy showed no chemical interaction and differential scanning calorimetry indicated endothermic peaks at 250 °C for pantoprazole sodium sesquihydrate. tmax for the test and reference formulations were 8 ± 2.345 h and 8 ± 2.305 h, respectively. Cmax of test and reference formulations were 46.026 ± 0.567 µg/mL and 43.026 ± 0.567 µg/mL, respectively. AUC(0-t) of the test and reference formulations were 472.115 ± 3.467 µg × h/mL and 456.105 ± 2.017 µg × h/mL, respectively. Raft forming system successfully delivered the drug in controlled manner and improved the bioavailability of drugs.

Design, Development and Evaluation of Dexamethasone Sodium Phosphate Niosomal in-situ Gel for Visual Medication Conveyance

The main purpose of this study was to beat issues related with lachrymal seepage by eye drops, obscured vision with semi solid formulation, distinctive framework was joined together as niosomes and in-situ gel by fusing niosomes in-situ gel formulation, so it is anything but difficult to controlled and hold at the site for drag out timeframe. The Dexamethasone sodium phosphate, a glucocorticosteroid anti-inflammatory drug utilized as a part of treatment of eye hypersensitive condition, keratitis, after eye surgery, post cataract treatment. Niosomes containing Dexamethasone sodium phosphate definitions were prepared by solvent injection technique using cholesterol alongside different surfactants proportions. Prepared Niosomal preparations were fused in-situ gel formulation plan by scattering the Niosomes in solution of carbomer 974 P (0.2-0.6% w/v) and Hydroxypropyl-methylcellulose (HPMC) K4M (0.5-0.8% w/v). Prepared formulations were assessed for their vesicle measure, entanglement proficiency, in-vitro sedate discharge, thickness, in-vitro gelation study and so on. From the results it can be concluded that by utilizing cholesterol: Tween-80 (1:2) proportion, particle size of Niosomes was B4 was 368.7 nm with 93.15% drug entrapment efficiency. In-vitro drug release kinetics from Niosomal in-situ gel definition demonstrates that 98.42% drug release in 6 hrs with the utilization of 0.8% w/v of HPMC K4M and 0.6% w/v of Carbomer 974 P. In conclusion, the Niosomal in-situ gel is a practical contrasting option to routine eye drops due to excellence of its capacity to improve bioavailability through its more drawn out residence time and capacity to sustain the drug release.

IN SITU GEL AS PLATFORM FOR KETOCONAZOLE SLOW RELEASE DOSAGE FORM

Objective: The aim of this study was to formulate ketoconazole (keto) as oral floating in situ gel to slow the release of keto in the stomach.Methods: Sodium alginate (Na alginate) was used as a primary polymer in the preparation of the in situ gel and was supported by the following polymers: guar gum (GG), hydroxypropyl methylcellulose (HPMC) K4M, K15M and carbapol 940 as viscosity enhancing agents. As a consequence, and to complete the gelation process of above formulations was by adding the calcium carbonate (CaCO3). The in situ gels were investigated by the following tests: floating lag time, floating duration, viscosity, drug content, in vitro gelling studies and in vitro release study.Results: The study showed that the faster release was obtained with F1 which contained Na alginate alone. Additionally, reduction in Na alginate concentration resulted in significant increase in drug release. It was also noted that the increase in GG (viscosity enhancing polymer) concentration resulted in non-significant decrease in percent drug release and the reduction in CaCO3 concentration led to significant increase in drug release. Moreover, the release of drug was also affected by grade of viscosity enhancing polymer, the faster release was observed with the formula which contained a polymer of low viscosity (HPMC K4M) and an opposite result was with the high viscosity polymer (HPMCK15M).Conclusion: This study showed the formulation of Na alginate with GG and CaCO3, led to gain floating in situ gel and a sustained release of keto.

FORMULATION AND EVALUATION OF PULSATILE DRUG DELIVERY SYSTEM OF SALBUTAMOL SULFATE FOR THE CHRONOTHERAPY OF ASTHMA

Objective: The main objective of the present study was to design and evaluate a time-controlled single unit oral pulsatile drug delivery system containing salbutamol sulfate for the prevention of nocturnal asthma attacks.Methods: Drug containing core tablets (C1-C10) with different composition of superdisintegrants such as sodium starch glycolate, croscarmellose sodium, and crospovidone were prepared by direct compression technique. The fast disintegrating core tablet formulation was selected, and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic and hydrophilic polymers: Ethylcellulose-20 (EC-20), hydroxypropyl methylcellulose K4M, and low substituted hydroxypropyl cellulose (L-HPC LH11). The coating polymers were selected and quantified based on in vitro lag time and drug release profile in simulated gastric and intestinal fluids.Results: Formulation C10 with 7.5% crospovidone showed least disintegrating time, i.e., 0.31 min and was selected as the best immediate release core tablet. The press-coated tablet formulation P11 having 360 mg barrier layer of EC-20 and L-HPC LH11 in ratio 14:1 over the core tablet C10 showed rapid and complete drug release nearly after 6 h lag time. Accelerated stability studies of the optimized formulation P11 indicated no significant difference in release profile after a period of 6 months.Conclusion: The in vitro dissolution study showed that lag time before drug release was highly affected by the coating level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques.

High-shear granulation of high-molecular weight hypromellose: effects of scale-up and process parameters on flow and compaction properties

Context: Knowledge of the effects of high-shear granulation process parameters and scale-up on the properties of the produced granules is essential for formulators who face challenges regarding poor flow and compaction during development of modified release tablets based on high-molecular weight hypromellose (hydroxypropylmethylcellulose (HPMC)) polymers. Almost none of the existing studies deal with realistic industrial formulation.Objective: The aim was to investigate the effects of scale-up and critical process parameters (CPPs) of high-shear granulation on the quality attributes of the granules, particularly in terms of the flow and compaction, using a realistic industrial formulation based on HPMC K100M polymer.Methods: The flow properties were determined using flow time, Carr index, tablet mass, and crushing strength variations. The compaction properties were quantified using the ‘out-of-die’ Heckel and modified Walker models, as well as the tensile strength profile and elastic recovery. High-shear granulation was performed at different scales: 4 L, 300 L, and 600 L.Results and conclusion: The scale itself had larger effects on the granule properties than the CPPs, which demonstrated high robustness of formulation on the individual scale level. Nevertheless, to achieve the desired flow and compaction, the values of the CPPs need to be precisely selected to fine-tune the process conditions. The best flow was achieved at high volumes of water addition, where larger and more spherical granules were obtained. The CPPs showed negligible influence on the compaction with no practical implications, however, the volume of water addition volume was identified as having the largest effects on compaction.

Formulation and in vitro evaluation of a thermoreversible mucoadhesive nasal gel of itopride hydrochloride

Itopride hydrochloride (ITO HCl) is a prokinetic agent, used in the treatment of gastrointestinal motility disorders. The aim of the study was to develop stable mucoadhesive thermoreversible nasal gel to avoid first pass effect. ITO HCl was incorporated into the blends of thermoreversible polymers like poloxamer 407 and various mucoadhesive polymers in different concentrations to increase the contact of the formulations with nasal mucosa. The compatibility between the drug and the suggested polymers was studied by Fourier transform infrared and differential scanning calorimetry (DSC). The formulations were evaluated for clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, and drug content. In addition, the in vitro drug release and the dissolution efficiency (DE)% were measured. The optimized formulations that showed the highest dissolution efficiency% (DE%) in saline phosphate buffer of pH 6.4 at 35 ± 0.5 °C were chosen for stability testing at temperatures of 4 ± 2 and 25 ± 2 °C/60 ± 5% RH. It was found that F1 and F17 that contain 18% w/v poloxamer 407 and 0.5% w/v of hydroxypropylmethyl cellulose K4M or methyl cellulose (MC), respectively, showed higher stability results as indicated by their higher t90 values (days).

Buccoadhesive gel of carvedilol nanoparticles for enhanced dissolution and bioavailability

The aim of the work was to improve carvedilol bioavailability through preparation of nanoparticles to be formulated as a buccoadhesive gel. Physicochemical compatibility of drug was studied. The ionic gelation technique was used for nanoparticles preparation based on 31 × 41 factorial design using Eudragit® RS100 as a complexing agent. Particle size, entrapment efficiency and dissolution parameters were measured and the formula of choice was prepared into two nanoparticles gel formulae to study the effect on bioavailability. The nanoparticles appearance was spherical and uniform. The tested formula variables significantly affected all the parameters (P value < 0.05). The particle size of the prepared formulae ranged from 150 to 225 nm and entrapment efficiency varied from 73.3 to 98.8%. The prepared gel formulae showed an acceptable bioadhesion force which is required for buccal application. Regarding pharmacokinetics parameters, both gel formulae shorten the Tmax from 1.5 h to 1 h compared to the market product. Carvedilol nanoparticles were successfully formulated using the ionic gelation technique with low particle size and high entrapment efficiency. The prepared nanoparticles gel contains both sodium carboxymethyl cellulose and hydroxypropyl methylcellulose K4M polymers showed two fold increase in relative bioavailability.

Effect of lipid and cellulose based matrix former on the release of highly soluble drug from extruded/spheronized, sintered and compacted pellets

BackgroundThe study was to develop an extended release (ER) encapsulated and compacted pellets of Atenolol using hydrophobic (wax based and polymeric based) and high viscosity grade hydrophilic matrix formers to control the release of this highly water soluble drug by extrusion/spheronization (ES). Atenolol is used for cardiovascular diseases and available as an immediate release (IR) tablet dosage form. The lipids, Carnauba wax (CW), Glyceryl monostearate (GMS) and cellulose based i.e. Hydroxypropyl methylcellulose (HPMC) and Ethyl cellulose (EC) were used in preparing Atenolol ER pellets. Thermal sintering and compaction techniques were also applied to control the burst release of Atenolol.MethodFor this purpose, thirty-six trial formulations (F1-F36) were designed by Response Surface Methodology (RSM), using Design-Expert 10 software, keeping (HPMC K4M, K15 M & K100 M), (EC 7FP, 10FP & 100FP), waxes (GMS, & CW), their combinations, sintering temperature and duration, as input variables. Dissolution studies were performed in pH, 1.2, 4.5 and 6.8 dissolution media. Drug release kinetics using different models such as zero order, first order, Korsmeyer-Peppas, Hixon Crowell, Baker-Lonsdale and Higuchi kinetics were studied with the help of DDsolver, an excel based add-in program.ResultsThe formulations F35 and F36 showed compliance with Korsmeyer-Peppas Super case II transport model (R2 = 0.975–0.971) in dissolution medium pH 4.5. No drug excipient interaction observed by FTIR. Stereomicroscopy showed that sintered combination pellets, (F35), were highly spherical (AR = 1.061, and sphericity = 0.943). The cross-sectional SEM magnification (at 7000X) of F34 and F35 showed dense cross-linking. The results revealed that the optimized formulations were F35 (sintered pellets) and F36 (compacted pellets) effectively controlling the drug release for 12 h.ConclusionExtended-release encapsulated, and compacted pellets were successfully prepared after the combination of lipids CW (10%) and GMS (20%) with EC (10FP 20% & 100FP 20%). Sintering and compaction, in addition, stabilized the system and controlled the initial burst release of the drug. Extended release (ER) Atenolol is an effective alternative of IR tablets in controlling hypertension and treating other cardiovascular diseases.

FORMULATION AND EVALUATION OF FLOATING MATRIX TABLETS OF LEVOFLOXACIN HEMIHYDRATE USING HYDROXYPROPYL METHYLCELLULOSE K4M TO TREAT HELICOBACTER PYLORI INFECTION

Objective: The aim of the study was to develop a floating drug delivery system of levofloxacin (LVF) hemihydrate for sustained drug delivery to improve the extended retention in the stomach, oral bioavailability, and local site-specific action in the stomach. Methods: Preparation of LVF tablets using melt granulation method using hydroxypropyl methylcellulose (HPMC) K4M with sodium bicarbonate as gas generating agent. From LFTA1 to LFTA5, formulations were developed and evaluated for floating properties for swelling characteristics and in vitro drug release studies. In vitro dissolution was carried out using USP II paddle method using 0.1N HCI pH buffer at 50 rpm and samples were measured at 294 nm using ultraviolet-visible spectroscopy. Results: Obtained Fourier-transform infrared charts indicated that there is no positive evidence for the interaction between LVF and ingredients of the optimized formula. In vitro drug release was performed and drug release kinetics were evaluated using the linear regression method and were found to be followed the zero-order release by diffusion controlled release. Optimized formula was found to be LFTA4 with 20% of a polymer with 99.03% of drug release with 12 h of floating time and 32 s floating lag time. Conclusion: Matrix tablets (LFTA4) formulated employing 20% HPMC K4M are best suited to be used for gastroretentive dosage form of LVF.

Formulation and evaluation of thermoresponsive polymeric blend as a vaginal controlled delivery system

Thermoresponsive polymers have the ability to undergo rapid changes in response to subtle environmental conditions and make stimuli-responsive materials attractive. They are candidates for minimally invasive, targeted and personalized drug delivery applications. Curcumin (CUR) is a phytochemical compound characterized by its low intrinsic toxicity and a wide variety of therapeutic effects. The modulating of the viscoelastic properties and bioadhesive characteristics of the thermoresponsive hydrogel (poloxamer 407) was achieved using a ternary system formed with chitosan and hydroxypropylmethylcellulose K4M (M20). The curcumin in solid dispersion form (CUR-SD) was used in the hydrogel preparation. The physical–chemical, physiomechanical, oxidative stress properties and antioxidant activity were evaluated and compared. Curcumin in SD form is more soluble and stable than in the physical mixture (PM) or free form. The transition from liquid to gel (Tsol–gel) temperature of the M20-SD formulation occurred at 36 °C. The CUR delivery profiles followed the Hixson–Crowell’s model. The M20-SD formulation showed antioxidant activity and as a strong inhibitor of oxidative stress. Analysis of results suggests that CUR-SD thermoresponsive hydrogel can be used via to the vaginal route for the treatment of mucosal inflammation and infectious disease, including HPV. The elastomeric hydrogel is formed by covalently cross-linked long and flexible polymer chains aggregated with water. The analysis results showed that M20-SD could remain at the application site for a sufficient time to permit the controlled delivery and to improve the therapeutic activity of CUR.